Vigabatrin

Identification

Name

Vigabatrin

Accession Number

DB01080 (APRD00282)

Type

Small Molecule

Groups

Approved

Description

An analogue of gamma-aminobutyric acid, vigabatrin is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed). Off-label uses include treatment of cocaine dependence.

Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a Ki of 10 mM.

Mechanism of action

Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active.

Rapidly absorbed following oral administration, absorption is comparable between neonates, infants, and children.
Cmax, 50 mg/kg dose, neonates= 14 mg/L;
Tmax, 50 mg/kg dose, neonates = 2.1 hours;
However, extent of absorption is higher and elimination half life is longer in neonates compared to children and infants. This is because neonates have reduced renal function compared to the aforementioned population groups.
AUC, 50 mg/kg dose, neonates = 142.6 ± 44.0 mg/L/hr;
Food may slightly decrease the rate (Cmax decreased by 33%, Tmax increased to 2 hours), but not the extent of absorption. Furthermore, vigabatrin does not cross the blood-brain-barrier well, thus high doses are needed.

Volume of distribution

1.1 L/kg

Protein binding

Not protein bound

Metabolism

Almost no metabolic transformation. Does not induce the hepatic cytochrome P450 system.